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• W2904861330 abstract "Huntington disease (HD) is a rare genetic neurodegenerative condition. The availability of a genetic diagnosis makes HD an attractive model for the development of therapies that can delay or, at best, halt the progression of neurodegenerative conditions. Tetrabenazine and deutetrabenazine are the only treatment options with a formal indication (chorea) for this patient population.Literature review on HD and clinical trials using the medical databases Pubmed, Web of Science, and clinical trial registries. Recent clinical trials conducted with the goal of disease-modification or new symptomatic treatment indications were included. Non-pharmacological interventions were excluded.Therapeutic approaches aiming at disease-modification include huntingtin-lowering strategies, the modulation of huntingtin homeostasis and neuroinflammation. Huntingtin-lowering strategies are of particular interest by targeting the mRNA of the huntingtin (HTT) gene at the core of HD biology. Antisense oligonucleotides (ASO) are the only huntingtin-lowering strategies in clinical development. The initial results suggest that the first non-allele specific ASO was safe and associated with a reduction in the levels of mutated huntingtin protein (mHTT). Other clinical trials for disease-modification in HD have generated negative results or are ongoing. Assays to measure CSF mHTT and brain nuclear imaging specific to HD can support the rational development of these therapies. Novel symptomatic treatment indications explored in clinical trials include motor disability, irritability and apathy.The years ahead are promising for novel and revolutionary therapies aimed at core disease mechanisms in HD. Clinical research platforms such as Enroll-HD are expected to potentiate the conduction of clinical trials in HD." @default.
• W2904861330 created "2018-12-22" @default.
• W2904861330 creator A5067113888 @default.
• W2904861330 date "2019-02-01" @default.
• W2904861330 modified "2023-10-07" @default.
• W2904861330 title "Recent advances in the therapeutic development for Huntington disease" @default.
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• W2904861330 doi "https://doi.org/10.1016/j.parkreldis.2018.12.003" @default.
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